Cryofibrinogen-associated glomerulonephritis accompanied by advanced gastric cancer

Abstract

We had a 72-year-old man with advanced gastric cancer, poorly differentiated adenocarcinoma, receiving chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) plus oxaliplatin. Ascites developed despite remission of gastric cancer and metastasis. Given no malignant cells in ascites, leg edema, renal impairment, hypoalbuminemia, and massive proteinuria, we diagnosed as nephrotic syndrome with microscopic hematuria. Renal biopsy showed membranoproliferative glomerulonephritis with no deposition of immunoglobulins and complements. Of note, electronic microscopy found organized deposits with microtubular structures in the glomerular capillary lumens and subendothelial spaces. The liquid chromatography-tandem mass spectrometry method detected fibrinogen alpha chain, beta chain, gamma chain, and fibronectin, and we eventually diagnosed cryofibrinogen-associated glomerulonephritis. Cryofibrinogen was not detected in plasma. He was expired at 5 months following renal biopsy due to the progression of refractory nephrotic syndrome. In addition to the detailed assessment of specifically organized deposits, the analysis using liquid chromatography-tandem mass spectrometry method is useful to diagnose cryofibrinogen-associated glomerulonephritis. We should consider cryofibrinogen-associated glomerulonephritis as a differential diagnosis when the patients with malignancy showed abnormal urinalysis and renal impairment, though it is a rare disease.

Discontinuing Hemodialysis through Corticosteroid Treatment in a Patient with Cryofibrinogen-associated Glomerulonephritis

“…In our case, proteinuria went into clinical remission, while hematuria persisted, and its degree remained unchanged for at least 19 months after corticosteroid therapy. Like our case, all six previously reported cases [please check this carefully] showed MPGN-like glomerulonephritis, and subendothelial deposition of cryofibrinogen exhibiting large fibrils with tubular structures was confirmed in five cases (2,(4)(5)(6).…”

“…However, in our case, the characteristic formation of large subendothelial fibrils was a limited finding and was only detected in the second kidney biopsy, in contrast to the global glomerular changes. Notably, some cases exhibit a segmental pattern of fibrinogen staining, similar to our case, despite the overall glomerular changes observed in those cases (2,4,5). The contribution of thrombotic vasculopathy by cryofibrinogen (7) was also unclear in our case of Cry-oFiGN.…”

“…Although we were unable to confirm the presence of cryofibrinogen in our patient's plasma, we diagnosed the patient with CryoFiGN based on the clinical presentation, MPGN-like glomerulonephritis without immunoglobulin depositions but with fibrinogen depositions, absence of electron-dense deposits, presence of subendothelial large fibrils with tubular structures, and evidence of fibrinogen depositions by LC-MS/MS. Immunotactoid glomerulonephritis also shows large microtubular substructures, but their diameters are up to 90 nm, and large tubular structures in CryoFiGN have diameters ranging from 40 to 50, 60, or 121 to 220 nm with multilamellar tubular structures similar to those in our case (2,(4)(5)(6). Awareness of the differential diagnosis of CryoFiGN in patients with MPGN-like glomerulonephritis without immunoglobulin deposition is important.…”

“…To our knowledge, only six other cases [please check this carefully] of CryoFiGN have been reported in detail in the English literature (2,(4)(5)(6)8). Clinical manifestations of Cry-oFiGN are variable and can range from asymptomatic proteinuria to nephritic syndrome or rapidly progressive glomerulonephritis (8,9).…”

Type VI collagen-related nephropathy

“…However, a proteomic analysis was not performed in one report [ 5 ] and immunohistochemical staining of type VI collagen was negative in the other report [ 6 ]. In contrast, a proteomic analysis in the case of cryofibrinogen-associated glomerulonephritis identified collagen α3 (VI) chain [ 4 ]. Although the details concerning the mechanism underlying the glomerular deposition of type VI collagen are unclear, the diagnosis in the present case was type VI collagen-related nephropathy.…”